MiR-20a-5p functions as a potent tumor suppressor by targeting PPP6C in acute myeloid leukemia.

Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.

The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer.

PURPOSE: The aim of this study was to investigate the antitumor effect of chidamide in combination with bortezomib on gastric cancer cell lines. MATERIALS AND METHODS: First, the sensitivity and IC50 values of chidamide and bortezomib in several gastric cancer cell lines (MGC-803, BGC-823, SGC-7901, and MKN45) were measured using the CCK-8 assay. Then, the relatively insensitive gastric cancer cell lines (MGC-803 and BGC-823) were treated with low concentrations of chidamide alone, bortezomib alone, or chidamide and bortezomib combination to detect the effects on cell proliferation, apoptosis, migration, and invasion. Finally, the inhibitory effect of the combined chidamide and bortezomib treatment on MGC-803 cells was verified in vivo through tumor formation experiments in nude mice. RESULTS: Compared with low-dose chidamide or bortezomib alone, the low-dose drug combination significantly inhibited the proliferation, migration, and invasion of MGC-803 and BGC-823 cells and induced apoptosis of the cells. The effects of the low-dose chidamide and bortezomib combination reduced the growth on gastric cancer in vivo were investigated by using a subcutaneous tumor mouse model. CONCLUSION: Our results suggest that the combination of chidamide and bortezomib can significantly reduce the proliferation, invasion, and migration of MGC-803 and BGC-823 cells, providing a framework for the clinical evaluation of combined therapies for gastric cancers.

Mammography-based radiomics nomogram: a potential biomarker to predict axillary lymph node metastasis in breast cancer.

OBJECTIVE: To establish a radiomics nomogram by integrating clinical risk factors and radiomics features extracted from digital mammography (MG) images for pre-operative prediction of axillary lymph node (ALN) metastasis in breast cancer. METHODS: 216 patients with breast cancer lesions confirmed by surgical excision pathology were divided into the primary cohort (n = 144) and validation cohort (n = 72). Radiomics features were extracted from craniocaudal (CC) view of mammograms, and radiomics features selection were performed using the methods of ANOVA F-value and least absolute shrinkage and selection operator; then a radiomics signature was constructed with the method of support vector machine. Multivariate logistic regression analysis was used to establish a radiomics nomogram based on the combination of radiomics signature and clinical factors. The C-index and calibration curves were derived based on the regression analysis both in the primary and validation cohorts. RESULTS: 95 of 216 patients were confirmed with ALN metastasis by pathology, and 52 cases were diagnosed as ALN metastasis based on MG-reported criteria. The sensitivity, specificity, accuracy and AUC (area under the receiver operating characteristic curve of MG-reported criteria were 42.7%, 90.8%, 24.1% and 0.666 (95% confidence interval: 0.591-0.741]. The radiomics nomogram, comprising progesterone receptor status, molecular subtype and radiomics signature, showed good calibration and better favorite performance for the metastatic ALN detection (AUC 0.883 and 0.863 in the primary and validation cohorts) than each independent clinical features (AUC 0.707 and 0.657 in the primary and validation cohorts) and radiomics signature (AUC 0.876 and 0.862 in the primary and validation cohorts). CONCLUSION: The MG-based radiomics nomogram could be used as a non-invasive and reliable tool in predicting ALN metastasis and may facilitate to assist clinicians for pre-operative decision-making. ADVANCES IN KNOWLEDGE: ALN status remains among the most important breast cancer prognostic factors and is essential for making treatment decisions. However, the value of detecting metastatic ALN by MG is very limited. The studies on pre-operative ALN metastasis prediction using the method of MG-based radiomics in breast cancer are very few. Therefore, we studied whether MG-based radiomics nomogram could be used as a predictive biomarker for the detection of metastatic ALN.

MicroRNA-33b regulates sensitivity to daunorubicin in acute myelocytic leukemia by regulating eukaryotic translation initiation factor 5A-2.

In this study, we aimed to study the effect of miR-33b in regulating sensitivity to daunorubicin (DNR) in acute myelocytic leukemia (AML). We used quantitative real-time polymerase chain reaction and Cell Counting Kit-8 assay to detect the level of miR-33b and cell viability. Cell apoptosis and the expression of eIF5A-2 and MCL-1 protein were detected by flow cytometry analysis and Western Blot analysis, respectively. MiR-33b mimic increased sensitivity of AML cells against DNR, while miR-33b inhibitor had the opposite effect. Furthermore, the results showed that the eIF5A-2 gene was a direct target of miR-33b, and miR-33b regulated eIF5A-2 mRNA and protein expression. Silencing of eIF5A-2 by RNA interference increased the sensitivity of AML cells against DNR. We also found that MCL-1 contributed to the regulation of DNR sensitivity, which was dependent on downregulation of eIF5A-2. Finally, knockdown of eIF5A-2 eliminated the effects of miRNA-33b mimic or inhibitor on DNR sensitivity. These findings indicate that miR-33b maybe as a new therapeutic target in AML cells.

miR-9 Enhances the Chemosensitivity of AML Cells to Daunorubicin by Targeting the EIF5A2/MCL-1 Axis.

Daunorubicin (Dnr) is at the forefront of acute myeloid leukemia (AML) therapy, but drug resistance poses a major threat to treatment success. MicroRNA (miR)-9 has been shown to have a pivotal role in AML development. However, little is known about the role of miR-9 in Dnr resistance in AML. We explored the potential role of miR-9 in Dnr resistance in AML cells and its mechanism of action. AML cell lines with high half-maximal inhibitory concentration to Dnr in vivo had significantly low miR-9 expression. miR-9 overexpresssion sensitized AML cells to Dnr, inhibited cell proliferation, and enhanced the ability of Dnr to induce apoptosis; miR-9 knockdown had the opposite effects. Mechanistic studies demonstrated that eukaryotic translation initiation factor 5A-2 (EIF5A2) was a putative target of miR-9, which was inversely correlated with the expression and role of miR-9 in AML cells. miR-9 improved the anti-tumor effects of Dnr by inhibiting myeloid cell leukemia-1 (MCL-1) expression, which was dependent on downregulation of EIF5A2 expression. These results suggest that miR-9 has an essential role in Dnr resistance in AML cells through inhibition of the EIF5A2/MCL-1 axis in AML cells. Our data highlight the potential application of miR-9 in chemotherapy for AML patients.

CT and clinical findings of peripheral primitive neuroectodermal tumour in children.

OBJECTIVE: To describe the clinical, CT and pathological findings of paediatric peripheral primitive neuroectodermal tumours (pPNETs) to enhance the recognition of these rare tumours. METHODS: The clinical, CT and pathological findings of 18 paediatric patients with pPNETs confirmed by biopsy or surgical pathology were retrospectively reviewed. RESULTS: The age of these 18 paediatric patients with pPNETs ranged from 4 months to 15 years, with a mean age of 7.7 years. The lesions of these 18 paediatric patients with pPNETs were located in the head and neck (n = 4), chest (n = 2), abdomen and pelvic cavity (n = 6), spine (n = 3), ilium (n = 2) and femur (n = 1). Immunohistochemical examination revealed Homer-Wright rosettes in seven lesions, and 94.4% of lesions showed consistent positive staining for CD99. On plain CT images, the majority of pPNETs showed lesions that were ill-defined (72.2%), irregularly shaped (83.3%), heterogeneous (66.7%) or hypodense masses (94.4%), and together with osteolytic bone destruction when the lesion originated in the bone. Calcifications were found in three lesions. After contrast administration, all soft-tissue masses were persistently enhanced heterogeneously with various cystic or necrotic regions, and 71.4% of them had linear enhancement. 94.4% of soft-tissue masses showed a moderate degree of enhancement. Seven cases had lymph node metastasis at diagnosis. CONCLUSION: Paediatric pPNET can involve any part of the body, and a large, ill-defined, aggressive soft-tissue mass and moderate heterogeneous enhancement with varying cystic regions and linear enhancement, with or without osteolytic bone destruction, on CT images could suggest the diagnosis. ADVANCES IN KNOWLEDGE: Primitive neuroectodermal tumours constitute a rare type of malignant neuroectodermal tumours that have chromosomal translocations identical to Ewing's sarcoma, and reports about radiological characteristics of this disease in children are insufficient. This study has described the clinical features and CT and pathological findings in 18 paediatric patients diagnosed with pPNETs in different locations, as a way to enhance the recognition of these tumours and help to differentiate from other types of paediatric malignant bone and soft-tissue tumours.

Pediatric Cryptococcal Lymphadenitis in the Absence of AIDS: Case Report and Literature Review.

We present a rare case of cryptococcal lymphadenitis without immunocompromization in a two-and-a-half-year-old child. He was referred to our center with a fifteen-day history of continued fever. Ultrasound and computed tomography (CT) revealed the enlargement of multiple lymph nodes and lung reticulonodular shadows. Hematological, immunological, and microbiological tests for hepatitis, lymphoma, AIDS, and immunoglobulin deficiencies were negative. Laboratory tests demonstrated elevated erythrocyte sedimentation rate, elevated plasma and urinary ß2-microglobulin (ß2-MG) levels, and elevated C-reactive protein and fibrinogen. Both blood routine and bone marrow aspiration showed elevated eosinophil granulocytes. The diagnosis of cryptococcal lymphadenitis was obtained by excisional biopsy of the cervical lymph nodes. The patient was treated with intravenous amphotericin B and oral flucytosine for five weeks, then with subsequent oral fluconazole for three months. The patient is now doing well. Our case suggests that the diagnosis of cryptococcal lymphadenitis is very difficult without etiology and pathology, especially for a patient with a normal immune system; lymph node biopsy is necessary to diagnose it, and immediate antifungal treatment is necessary to treat it.